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Identification of ALDOA as a new Lung adeonocarcinoma predict gene involve cancer metabolism and tumor metastasis
Author(s) -
Chang Yuchan,
Jan YiHua,
Chan YungChieh,
Yang YiFang,
Su ChiaYi,
Lai TsungChing,
Liu YuPeng,
Hsiao Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.58.1
Subject(s) - gene knockdown , biology , lung cancer , cancer research , metastasis , tissue microarray , glycolysis , cancer , aldolase a , cancer cell , gene , pathology , genetics , enzyme , medicine , biochemistry
The metabolic alterations in cancer progression remain unknown. In this study, we identified Aldolase A (ALDOA), a glycolytic enzyme that regulates glycolysis process, as the most significant marker in lung cancer by comparative microarray and prognosis database analysis. We observed overexpression of ALDOA mRNA was significantly associated with poor overall survival rate with the hazard ratio of (HR=3.0, P<0.01). Microarray datasets also showed high ALDOA expression in tumor compared with corresponding normal tissue in 27 lung cancer patient (p<0.01). Strong expression of ALDOA protein by IHC was further detected in 94.3% cases (99/105) and the expression level was higher compared to non‐tumor lung parenchyma (p<0.01). High ALDOA expression was found associated with poor survival (p<0.01) of lung cancer patients. ALDOA overexpression promoted invasion and migration in vitro. These complementary function expression consequences were also validated in metastasis colony forming assay in vivo and in‐situ invasion assay. Furthermore, overexpression of ALDOA induces upregulation of GAP1, and MMP2. Knockdown of GAP or MMP2 inhibited ALDOA induced invasion and migration in vitro, suggesting that ALDOA may promote lung cancer cell matastasis by the activation of GAP and MMP2. Our finding may implicate the possibility of targeting ALDOA as a novel therapeutic strategy to inhibit lung cancer metastasis.